The present invention relates to a synthesis experiment automation system for automating chemical synthesis experiments, and to a liquid level/interface position detecting device, a separation processing device, and a reaction container, which are suitable for use in the synthesis experiment automation system.
In the past, various automated experiment devices have been developed in order to increase the efficiency of chemical experiments and reduce the effort involved therein.
Automated experiment devices of this kind can be broadly divided into, for example, (1) devices which control reaction conditions by, for example, controlling temperature, pressure, flow, etc., precision measuring of heat balance, and analyzing reaction parameters; (2) sequential devices for synthesizing samples of small quantity by performing synthesis, post-processing, refinement, etc.; and (3) devices which use a robot to perform synthesis, post-processing, and analysis.
Specific examples of these kinds of automated experiment devices are (I) synthesis reaction devices such as those disclosed in Japanese Unexamined Patent Publication Nos. 1-249135/1989 (Tokukaihei 1-249135), 2-2870/1990 (Tokukaihei 2-2870), 6-63389/1994 (Tokukaihei 6-63389), and 6-79166/1994 (Tokukaihei 6-79166); (II) automated synthesis devices such as the Contalab (manufactured by Mettler Co.) and the ARS (manufactured by Sogo Chemical Industries Co., Ltd.); and (III) the synthesis experiment device CombiTec (manufactured by Tecan Co.), which uses a robot.
However, the synthesis reaction devices in (I) above are integral sequence control devices, which conduct a reaction in a single location by introducing reagents, solvents, etc. into a pre-set reaction container. For this reason, with these devices, the system has little flexibility or extendibility, and since the location of the reaction is limited, it is difficult to conduct several reactions simultaneously or freely rearrange the reaction process.
Again, the automated synthesis devices in, (II) above can only perform a single reaction in a single reaction device, and thus have the drawback that only one reaction can be conducted at a time.
Since the synthesis experiment device in (III) above uses a robot, it has more extendibility than the devices in (I) or (II), but since the number of possible experiment unit operations is small, it is unable to perform complex synthesis experiments which combine a plurality of unit operations.
In each of the foregoing conventional automated devices, a machine performs operations formerly performed by humans. However, these conventional automated devices have several problems, such as inability to perform several experiments simultaneously, a limited number of reagents which can be supplied automatically, a narrow reaction temperature range, a limited number of possible experiment unit operations, difficulty of improvement or extension of the device, etc. Accordingly, these conventional automated devices cannot be said to have dramatically reduced the effort or improved the efficiency of chemical experiments.
Further, with organic synthesis reactions, there are many cases in which the reaction produces a solution phase made up of at least two incompatible solutions. In such a case, the desired compound must be separated out from the reaction container.
With this kind of solution phase made up of two incompatible solutions which have separated into layers, separation processing to separate out each solution is often carried out in extraction processing, in which a desired compound is separated out from a reaction liquid obtained by, for example, an organic synthesis reaction. A separation funnel is often used for this separation processing.
In separation processing using a separation funnel, the operator separates the two solutions by, first, visually checking the liquid level of the solution phase which has separated into layers and the interface between the two solution layers, and then, in accordance with the liquid level and interface, extracting from the separation funnel one of the solutions of the solution phase, after which, as necessary, the other solution remaining in the separation funnel may be extracted into another container.
However, in using a separation funnel to separate out each solution from this kind of solution phase made up of two incompatible solutions which have separated into layers, the operator must check the positions of the liquid level of the solution phase and the interface between the two solutions, as well as perform the operations for separating out each solution.
Accordingly, in conventional separation processing using a separation funnel, since the separation processing itself is carried out by the operator, the operator must be used to operating with a separation funnel in order to perform the separation processing correctly. In other words, if the operator is not used to operating with a separation funnel, when the difference in color of the two solutions in the solution phase is subtle, it is difficult to correctly distinguish the interface, and the operator may not be able to correctly separate out the solutions of the solution phase.
Since the operations of the above-mentioned separation funnel are manual, it has been difficult to use in conventional devices which perform organic synthesis reactions automatically, and this has made automation of organic synthesis reactions difficult.
In conventional chemical experiments, when allowing two or more reagents to react in a reflux, reaction containers like that shown in FIG. 39 have been used (see Experimental Chemistry Lectures 2: Basic Operations II, 4th Ed., Maruzen Co., Ltd.).
The reaction container shown in FIG. 39 is made up of a flask 511 which contains a reagent C, a drip funnel 512 which contains a reagent D, a condenser 513, and a stirrer 514.
A reaction between the reagents C and D is conducted by dripping the reagent D from the drip funnel 512 into the flask 511 which contains the reagent C. This kind of reaction is often conducted with the application of heat, and reaction raw materials, reaction products, and reaction solvent vaporized by heating are cooled by the condenser 513, and are thus liquefied and returned to the flask 511. Further, in order to stabilize the reaction, stirring is usually performed using the stirrer 514.
In addition, this kind of reaction is usually performed with the reaction system sealed under open pressure by means of a filling tube filled with drying agent, etc. and attached to the top of the condenser 513.
In this way, in conventional reaction containers, the drip funnel 512, which is a reagent introducing member, the condenser 513, which is a cooling member, and the sealing member (not shown) were provided separately from the flask 511.
However, since the reagent introducing member, cooling member, and sealing member are provided separately, disadvantages of this kind of conventional reaction container are that the size of the container as a whole in increased, and that assembly of the container is troublesome.
Because of these problems, it has been difficult to use the above-mentioned conventional reaction container in conventional devices which perform organic synthesis reactions automatically, and this has made automation of organic synthesis reactions difficult.
The object of the present invention is to provide a synthesis experiment automation system which is capable of simultaneously performing a plurality of different experiments as complex as those usually performed by researchers, which has a large number of possible experiment operations, and which can be easily improved and/or extended.
Another object of the present invention is to provide a separation processing device which automatically detects a liquid level position and an interface position in a solution phase made up of two incompatible solutions which have separated into layers, and which automatically performs solution extraction operations based on the detected liquid level and interface positions.
A further object of the present invention is to provide a reaction container in which a reagent introducing section, a cooling section, and a sealing section are combined together, and which is compact and easy to assemble.
In order to attain the foregoing objects, the inventors, etc. of the present invention invented a synthesis experiment automation system, a separation processing device, and a reaction container, which are, collectively, capable of simultaneously performing a plurality of different experiments as complex as those usually performed by researchers, and which dramatically reduce the effort and improve the efficiency of chemical experiments.
Accordingly, in order to attain the foregoing objects, a synthesis experiment automation system according to the present invention is made up of:
(1) a reaction system which includes (a) a reaction container rack for storing a plurality of reaction containers, (b) a dispensing device for introducing reagents and solvents into the reaction containers, and (c) a reaction device having a plurality of reaction sections capable of holding a plurality of reaction containers into which reagents and solvents have been introduced, and which is capable of setting different experiment conditions for different reaction sections;
(2) a robot which removes reaction containers from the reaction container rack, transports the reaction containers to a dispensing position of the dispensing device, and transports reaction containers into which reagents and solvents have been introduced to a predetermined position in a reaction section of the reaction device; and
(3) a computer which controls the actions of the robot in transporting and placing the reaction containers and the operations of the devices in the reaction system, separately for each set of experiment conditions.
With the foregoing structure, since the computer controls the operations of the devices in the reaction system separately for each set of synthesis reaction experiment conditions, the reaction sections within the reaction device can be operated under different experiment conditions. For example, if each reaction section in the reaction device is provided with temperature regulating means which can be set to different temperatures, and if temperature regulating operations of these temperature regulating means are controlled by the computer, a plurality of synthesis reactions can be simultaneously carried out under different temperature conditions.
Further, since each reaction section is capable of holding a plurality of reaction containers, synthesis reactions can be carried out under an even greater number of different experiment conditions.
Again, since the actions of the robot in transporting and placing the reaction containers are also controlled by the computer, the robot transports the reaction containers within the reaction system in accordance with the experiment conditions of each synthesis reaction. For this reason, the synthesis experiment automated system can easily be extended by simply placing additional reaction system devices within the robot""s range of action.
In addition, since the actions of the robot in transporting and placing the reaction containers and the actions of the reaction system devices are controlled for the experiment conditions of each synthesis reaction, they can be flexibly tailored to various synthesis reactions, and the reaction process can be freely rearranged. This also improves the flexibility of the system as a whole.
In order to attain the foregoing objects, a separation processing device according to the present invention includes a reading means which reads an image of a solution phase made up of two incompatible solutions which have separated into upper and lower layers, a position detecting means which detects, from the image read by the reading means, the positions of the liquid level of the solution phase and the interface between the upper- and lower-layer solutions, and a solution extracting means which calculates the quantities of the upper- and lower-layer solutions on the basis of the results detected by the position detecting means, and extracts one or both of the upper- and lower-layer solutions of the solution phase.
With the foregoing structure, the position detecting means detects the positions of the liquid level and the interface from the image of the solution phase made up of two incompatible solutions which have separated into layers. Accordingly, operations for detecting the positions of the liquid level and the interface can be carried out automatically.
Further, the solution extracting means calculates the quantities of the upper- and lower-layer solutions on the basis of the results detected by the position detecting means, i.e., on the basis of the positions of the liquid level and interface detected by the position detecting means, and then extracts one or both of the upper- and lower-layer solutions. Accordingly, extraction of the solutions can also be automated.
Since the positions of the liquid level and the interface can be automatically detected by the position detecting means from the image of the solution phase read by the reading means, and each solution of the solution phase can be automatically extracted based on the results detected by the position detecting means, this separation processing device is suitable for use in a device for automatically performing organic synthesis reactions. This makes it easy to fully automate a device for automatically performing organic synthesis reactions.
In order to attain the foregoing objects, a reaction container according to the present invention is made up of:
(1) a container section, into which a first reagent is placed in advance; and
(2) an introducing tube which introduces a second reagent into the container section, and which includes:
(a) a cooling section having an inner tube, through which the second reagent is introduced, and an outer tube surrounding the outer wall of the inner tube, which cools a vaporized component passing through the inner tube by means of a cooling medium passed through the outer tube;
(b) a reagent introducing section which introduces the second reagent through an upper opening of the inner tube, and thence into the container section through a lower opening of the inner tube; and
(c) a sealing section which introduces a gas through a gas flow intake branching from the outer tube.
With the foregoing structure, in order to conduct a reaction between the first and second reagents, the first reagent is placed in the container section in advance. Next, the second reagent is introduced into the container section through the introducing tube. At this time, the second reagent passes through the inner tube of the introducing tube. A vaporized component produced in the container section during reaction attempts to escape through the inner tube of the introducing tube, but is cooled by the cooling medium (water, for example) passing between the inner tube and the wall of the outer tube, and is thus liquefied and returned to the container section. Further, in order to seal the container interior by isolating it from the atmosphere, an inert gas (nitrogen, for example) is introduced through a gas flow intake provided in the wall of the upper part of the introducing tube. This gas flows into and fills the upper part of the inner tube, and is released from the upper opening of the inner tube.
Incidentally, the first and second reagents referred to above are not necessarily single compounds, and in some cases may be mixtures of two or more compounds. Again, the first and second reagents may each be mixed with reaction solvents, or a reaction solvent may be placed in the container section in advance.
By means of the reaction container outlined above, the reagent introducing section, cooling section, and sealing section, which conventionally were provided separately on the container section, can be combined into a single member, and thus a reaction container can be obtained which is more compact, and which is easily assembled.
Accordingly, since assembly is easy, a reaction container with the foregoing structure is suited for use in an automated device.